1. Field of the Invention
The present invention relates to the treatment of atherosclerosis through adjunctive photodynamic therapy generally, and more particularly to the prevention of restenosis following atherectomy or angioplasty.
2. Prior Art
Atherosclerosis is a cardiovascular disease in which deposits of plaques (atheromas) containing cholesterol, lipid material, foam cells, lipophages and proliferating smooth muscle cells are within the intima and media of large to small diameter arteries such as the aorta and the iliac, femoral, coronary and cerebral arteries. The resultant stenosis causes reduction in blood flow.
Attempts to treat atherosclerosis have included by-pass surgery wherein the diseased vascular segments are augmented by prosthetic or natural grafts. This procedure requires general anesthesia and a substantial healing period after surgery and, thus, is generally limited to cases of severe coronary artery disease.
Other approaches for the recanalization of stenotic vessels include percutaneous transluminal coronary angioplasty (PTCA), atherectomy, stenting and newer modalities of cardiovascular intervention including laser angioplasty. The word "recanalization", as used herein, means a procedure for increasing blood flow through the occluded vessel by angioplasty, including dilation or ablation or removal of occlusive material. The primary drawbacks of these methods has been restenosis. Studies have shown that restenosis, or the re-narrowing, of the internal lumen of an artery subsequent to such recanalization occurs in about 25-50% of cases where such primary treatment is performed. The result of restenosis is the requirement for an additional interventional or surgical procedure.
Various mechanisms can cause re-stenosis. One mechanism is rapid smooth muscle cell (SMC) proliferation at the lesion site. Smooth muscle cell proliferation is believed to occur immediately or at any time up to several hours after vessel wall injury that results from primary atherosclerotic treatment such as angioplasty. This proliferation continues for about 5-18 days depending on the individual. The cause of this rapid smooth muscle cell proliferation is believed to involve the release of various growth factors in response to the vessel wall injury. Specifically, after such vessel wall injury, some smooth muscle cells migrate to the intima where they are affected by the blood elements with which they come in contact, especially platelets and lipoproteins. Platelets contain a factor that stimulates smooth muscle cell proliferation and migration, which can result in re-stenosis.
March, et al., in U.S. Pat. No. 5,116,864 provides a method for preventing re-stenosis in a patient undergoing vascular recanalization. The method comprises the systemic administration of a photoactivatable psoralen compound, preferably by an oral route, to achieve serum levels around 1 .mu.M. Alternatively, the psoralen may be delivered to the tissue by intra-arterial injection through a catheter. Following psoralen administration, the atheroma is illuminated with ultraviolet radiation until recanalization is complete. This is where March, et al.'s treatment ends.
Other drugs are used to prevent restenosis. One such drug is heparin. Heparin is an anticoagulant which when delivered systemically severely reduces the ability of the body to form blood clots. Devices for preventing restenosis such as implantable stents require massive doses of heparin which requires the patient to remain hospitalized for a long period of time.
Stents are presently being investigated as a treatment for cardiovascular disease, Early results indicate that stents have a similar rate of restenosis when compared to conventional interventions with the added complication of abrupt closure of the vessel. Stents have also been used as a "bail out" device to maintain the patency of a collapsing artery until another corrective medical procedure can be performed. Stents are composed of many materials including stainless steel, biodegradable polymers, collagen, gelatin, etc.
Local drug delivery devices such as suppositories and dermal patches have been used as indwelling devices. Indwelling devices to treat cardiovascular disease through delivery of local drugs are not clinically available.
Accordingly, there is a need to address the problem of smooth muscle cell proliferation in the treatment of atherosclerosis to minimize or eliminate the occurrence of restenosis.